The Federal Women Study is an active clinical protocol aimed at recruiting 360 federal employees and contractors working in the Washington DC metropolitan area. One hundred and nine women (56% African-American, 17% African immigrant and 31% white) have been screened (age 449, range 24-62 years). Thirty percent of women had anemia and this was the most common reason that screened women were not enrolled. Among the enrolled women, the three groups are well matched by race/ethnicity for key socio-economic and demographic risk factors such as educational attainment, family history of diabetes and physical activity. Yet, we have already identified pre-diabetes in 39% of women (42% African-American, 13% African immigrant and 29% white). Therefore, this cohort reflects women who are at high risk for diabetes and heart disease and an excellent group in which to (a) test the efficacy of existing screening tests and (b) understand the pathophysiological progression of cardiometabolic disease by race/ethnicity. As current cardiometabolic screening tests are centered on triglyceride and fasting glucose concentrations, we have employed two approaches to examine these risk factors. The Relationship of Triglycerides with Insulin Resistance and Hyperinsulinemia This study will compare by race/ethnicty and continent of origin, the relationship of triglyceride concentration to key cardiometabolic risk factors, specifically diet, physical activity, insulin resistance (and hyperinsulinemia) and hepatic fat content. We have found so far that consistent with our hypothesis, fasting triglyceride concentrations are lowest in African immigrant and highest in white women (AI: 5312 vs. AA: 6733 vs. WW: 8334 mg/dL, P<0.01) with a trend for lower insulin sensitivity index (AI: 3.11.7 vs. AA: 2.51.6 vs. WW: 3.42.2 mU/L-1min-1, P=0.20) and greater acute insulin response to glucose (AI: 895528 vs. AA: 959790 vs. WW: 561429 mU/L, P=0.07) in African-American women. Analysis of the relationship of hepatic fat content with insulin resistance is underway. In regard to total percent fat there were no differences by race/ethnicity but differences in body fat distribution were clear, specifically visceral adipose tissue (VAT) volume (VAT; AI: 4836 vs. AA: 8642 vs. WW: 11854 cm3, P=0.001). To further characterize the contribution of insulin secretion, insulin clearance and prandial gut factors to race/ethnic differences in hyperinsulinemia, we are comparing insulin response to oral, intravenous and prandial glucose loads. Preliminary findings suggest racial differences in early postprandial glucose response. African descent women have paradoxically greater postprandial insulin concentrations but lower glucose response and we are exploring further the quantitative contribution of incretin concentrations to hyperinsulinemia. We plan to continue recruitment and look forward to an expanded dataset with interim analyses of our primary outcome variable, triglyceride concentration, with key modifying factors (diet composition, physical activity, insulin sensitivity indices and hepatic fat). These analyses should provide population-specific evidence which elucidate important pathophysiological pathways and ultimately lead to enhanced screening and diagnostic guidelines which have the potential to minimize diabetes related health disparities worldwide.